In a multivariate analysis that included tumor size and histology, type of surgery, and stage of disease, having baseline-stimulated thyroglobulin in the highest tertile was the sole factor that predicted persistence (OR 45.3, 95% CI 5.4-374.6), according to Cintia Gonzalez, MD, PhD, of Hospital Santa Creu i Sant Pau in Barcelona, and colleagues.

The optimal cutoff point for predicting remission at 18 to 24 months was 8.55 mcg/L, with a sensitivity of 88% and specificity of 72%, and with a positive predictive value of 47% and a negative predictive value of 95%, the researchers reported online in Clinical Endocrinology.

"Thyroglobulin measurement is one of the keystones of [differentiated thyroid carcinoma] management. It is essential to identify patients with residual tumor and to prevent unnecessary additional testing in those who are in remission," wrote Gonzalez and colleagues.

To assess the value of the test at the longer time interval, the researchers conducted a retrospective study of 133 patients with differentiated thyroid carcinoma treated between 1998 and 2010.

More than three-quarters were women, and mean age at the time of thyroidectomy was 47.

Stimulation of thyroglobulin was done according to standard protocols, with two intramuscular injections of 0.9 mg of recombinant thyroid stimulating hormone followed by measurement of thyroid stimulating hormone, thyroglobulin, and thyroglobulin antibodies.

An alternative method of stimulation was the withdrawal of thyroid hormone.

The baseline-stimulated thyroglobulin was measured just after thyroidectomy and before radioactive iodine remnant ablation was performed.

Disease was defined as persistent at 18 to 24 months if thyroglobulin could be detected or thyroglobulin antibodies were present, with imaging studies done as needed.

At the first post-surgery evaluation, between 6 and 12 months, thyroglobulin could be detected in 73 patients, 27 of whom also had positive findings on imaging studies.

Among the 46 patients with detectable thyroglobulin but negative imaging findings at 6 to 12 months, the thyroglobulin became undetectable by 18 to 24 months with no additional treatment.

Overall, by 2 years, disease persisted in 25.5% of patients. In 80% of these, structural manifestations could be seen, which in 76% of cases were loco-regional metastases. In the remaining 24%, there were distant metastases.

Receiver operating characteristic (ROC) curve analysis was used to determine the optimal cutoff for baseline-stimulated thyroglobulin.

This analysis determined that the area under the ROC curve was 0.872 (95% CI 0.791-0.952, P<0.001), the researchers reported.

A second multivariate analysis included patients with positive thyroglobulin antibodies, which can interfere with accurate measurement of thyroglobulin.

As in the primary multivariate analysis, having high levels of baseline-stimulated thyroglobulin independently predicted ongoing disease at 18 to 24 months in these patients (OR 39.6, 95% CI 4.7-334, P<0.001).

"An important result" of this study was the high (95.5%) negative predictive value of the cutoff 8.55 mcg/L for baseline-stimulated thyroglobulin, according to the researchers.

However, the low positive predictive value, similar to that seen in other studies, would be less helpful for detecting ongoing disease.

"In our view, this result is not so relevant as initial management strategies in these patients (total thyroidectomy with or without lymph node detection, [radioactive iodine remnant ablation], and suppressive therapy with levothyroxine) would not differ," the researchers explained.

Limitations of the study included its retrospective design and small patient population.

"Prospective studies are needed to demonstrate that radioactive iodine remnant ablation could be avoided in patients with baseline-stimulated thyroglobulin levels lower than 8.55 mcg/L," they concluded.

The study was supported by the Spanish Ministry of Health.

The authors reported no conflicts of interest.

Reviewed by F. Perry Wilson, MD, MSCE Instructor of Medicine, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner

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